498 research outputs found

    RNA trafficking and stabilization elements associate with multiple brain proteins

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    Two of the best understood somatic cell mRNA cytoplasmic trafficking elements are those governing localization of beta-actin and myelin basic protein mRNAs. These cis-acting elements bind the trans-acting factors fibroblast ZBP-1 and hnRNP A2, respectively. It is not known whether these elements fulfil other roles in mRNA metabolism. To address this question we have used Edman sequencing and western blotting to identify six rat brain proteins that bind the beta-actin element (zipcode). All are known RNA-binding proteins and differ from ZBP-1. Comparison with proteins that bind the hnRNP A2 and AU-rich response elements, A2RE/A2RE11 and AURE, showed that AURE and zipcode bind a similar set of proteins that does not overlap with those that bind A2RE11. The zipcode-binding protein, KSRP, and hnRNP A2 were selected for further study and were shown by confocal immunolluorescence microscopy to have similar distributions in the central nervous system, but they were found in largely separate locations in cell nuclei. In the cytoplasm of cultured oligodendrocytes they were segregated into separate populations of cytoplasmic granules. We conclude that not only may there be families of trans-acting factors for the same cis-acting element, which are presumably required at different stages of mRNA processing and metabolism, but independent factors may also target different and multiple RNAs in the same cell

    A prospective cohort study evaluating screening and assessment of six modifiable risk factors in HPB cancer patients and compliance to recommended prehabilitation interventions

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    INTRODUCTION: Despite improvements in perioperative care, major abdominal surgery continues to be associated with significant perioperative morbidity. Accurate preoperative risk stratification and optimisation (prehabilitation) are necessary to reduce perioperative morbidity. This study evaluated the screening and assessment of modifiable risk factors amendable for prehabilitation interventions and measured the patient compliance rate with recommended interventions.METHOD: Between May 2019 and January 2020, patients referred to our hospital for HPB surgery were screened and assessed on six modifiable preoperative risk factors. The risk factors and screening tools used, with cutoff values, included (i) low physical fitness (a 6-min walk test &lt; 82% of patient's calculated norm and/or patient's activity level not meeting the global recommendations on physical activity for health). Patients who were unfit based on the screening were assessed with a cardiopulmonary exercise test (anaerobic threshold ≤ 11 mL/kg/min); (ii) malnutrition (patient-generated subjective global assessment ≥ 4); (iii) iron-deficiency anaemia (haemoglobin &lt; 12 g/dL for women, &lt; 13 g/dL for men and transferrin saturation ≤ 20%); (iv) frailty (Groningen frailty indicator/Robinson frailty score ≥ 4); (v) substance use (smoking and alcohol use of &gt; 5 units per week) and (vi) low psychological resilience (Hospital Anxiety and Depression Scale ≥ 8). Patients had a consultation with the surgeon on the same day as their screening. High-risk patients were referred for necessary interventions.RESULTS: One hundred consecutive patients were screened at our prehabilitation outpatient clinic. The prevalence of high-risk patients per risk factor was 64% for low physical fitness, 42% for malnutrition, 32% for anaemia (in 47% due to iron deficiency), 22% for frailty, 12% for smoking, 18% for alcohol use and 21% for low psychological resilience. Of the 77 patients who were eventually scheduled for surgery, 53 (68.8%) needed at least one intervention, of whom 28 (52.8%) complied with 100% of the necessary interventions. The median (IQR) number of interventions needed in the 77 patients was 1.0 (0-2).CONCLUSION: It is feasible to screen and assess all patients referred for HPB cancer surgery for six modifiable risk factors. Most of the patients had at least one risk factor that could be optimised. However, compliance with the suggested interventions remains challenging.</p

    Discrimination of biofilm samples using pattern recognition techniques

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    Biofilms are complex aggregates formed by microorganisms such as bacteria, fungi and algae, which grow at the interfaces between water and natural or artificial materials. They are actively involved in processes of sorption and desorption of metal ions in water and reflect the environmental conditions in the recent past. Therefore, biofilms can be used as bioindicators of water quality. The goal of this study was to determine whether the biofilms, developed in different aquatic systems, could be successfully discriminated using data on their elemental compositions. Biofilms were grown on natural or polycarbonate materials in flowing water, standing water and seawater bodies. Using an unsupervised technique such as principal component analysis (PCA) and several supervised methods like classification and regression trees (CART), discriminant partial least squares regression (DPLS) and uninformative variable elimination–DPLS (UVE-DPLS), we could confirm the uniqueness of sea biofilms and make a distinction between flowing water and standing water biofilms. The CART, DPLS and UVE-DPLS discriminant models were validated with an independent test set selected either by the Kennard and Stone method or the duplex algorithm. The best model was obtained from CART with 100% correct classification rate for the test set designed by the Kennard and Stone algorithm. With CART, one variable describing the Mg content in the biofilm water phase was found to be important for the discrimination of flowing water and standing water biofilms

    Protocol for PIT: a phase III trial of prophylactic irradiation of tracts in patients with malignant pleural mesothelioma following invasive chest wall intervention.

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    INTRODUCTION: Histological diagnosis of malignant mesothelioma requires an invasive procedure such as CT-guided needle biopsy, thoracoscopy, video-assisted thorascopic surgery (VATs) or thoracotomy. These invasive procedures encourage tumour cell seeding at the intervention site and patients can develop tumour nodules within the chest wall. In an effort to prevent nodules developing, it has been widespread practice across Europe to irradiate intervention sites postprocedure--a practice known as prophylactic irradiation of tracts (PIT). To date there has not been a suitably powered randomised trial to determine whether PIT is effective at reducing the risk of chest wall nodule development. METHODS AND ANALYSIS: In this multicentre phase III randomised controlled superiority trial, 374 patients who can receive radiotherapy within 42 days of a chest wall intervention will be randomised to receive PIT or no PIT. Patients will be randomised on a 1:1 basis. Radiotherapy in the PIT arm will be 21 Gy in three fractions. Subsequent chemotherapy is given at the clinicians' discretion. A reduction in the incidence of chest wall nodules from 15% to 5% in favour of radiotherapy 6 months after randomisation would be clinically significant. All patients will be followed up for up to 2 years with monthly telephone contact and at least four outpatient visits in the first year. ETHICS AND DISSEMINATION: PIT was approved by NRES Committee North West-Greater Manchester West (REC reference 12/NW/0249) and recruitment is currently on-going, the last patient is expected to be randomised by the end of 2015. The analysis of the primary end point, incidence of chest wall nodules 6 months after randomisation, is expected to be published in 2016 in a peer reviewed journal and results will also be presented at scientific meetings and summary results published online. A follow-up analysis is expected to be published in 2018. TRIAL REGISTRATION NUMBER: ISRCTN04240319; NCT01604005; Pre-results
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